Since May 2022, doctors in 35 countries have found puzzling hepatitis in more than 1000 children: several children died, others needed a liver transplant. Among other things, adenoviruses were suspected. Two working groups from London and Glasgow are now assuming that adenoviruses have triggered the liver inflammation, as they report on the Preprint server Medrxiv and on the server of the NHS.
Both teams report that they have detected the complete genomes of adeno-associated virus 2 (AAV2) in the liver and blood of most of the patients examined. In addition, they identified two helper viruses that could allow the adenovirus to enter the liver cells and thus increase susceptibility. On the other hand, the parties exclude the adenovirus subtype 41F, which was previously considered as a potential trigger. They tracked down the AAV2 using so-called metagenomic sequencing. To do this, they sequenced all genes in the tissue or blood samples of affected children and then searched for the genetic material of viruses.
Emma Thomson from Glasgow Center for Virus Research and its working group pointed out AAV2 in all nine blood plasma samples and each of the four liver biopsies examined, which came from some of the first sick people who had been instructed to the children's clinic in Glasgow. In contrast, the tests in children with other infections or with hepatitis from a different cause were consistently negative. Sofia Morfopoulou from the Institute of Child Health at University College London and their team came to a similar result, five of whom needed a transplant.
AAV2 cannot replicate itself without outside help, but both working groups also demonstrated corresponding helpers: the HAdV and HHV6B, known as helper viruses. The latter in particular could pave the way for the adenovirus to enter the liver cells, Thomson suspects. There the main virus can then multiply and thereby apparently triggers the liver inflammation.
However, it is still unclear why the virus causes this serious illness frequently: Medicine has known AAV2 for almost 60 years, and four out of five adults have already been infected. This usually happens in early childhood and almost always runs without complications. In principle, adenoviruses only rarely lead to hepatitis.
Thomson and Co point out, however, that the virus has not yet been made visible under the electron microscope; in addition, there is no experimental evidence that it really infects the liver and causes damage there. Christina Pagel, a physician at the Clinical Operational Research Unit in London, also points out that while this is a strong correlation, it is not yet definitive evidence. Further studies are urgently needed.
